151: Better leukemia drugs prevent cancer from evolving

Gleevec shuts down CML by blocking the function of Bcr-Abl, the abnormal tyrosine kinase protein in the leukemic cells that causes them to grow too quickly. However, it does not bind very tightly to this protein, takes a long time to induce remissions, and patients can develop a resistant type of Bcr-Abl that no longer binds to Gleevec at all.

To circumvent these shortcomings, researchers at Novartis determined the crystal structure of Bcr-Abl, and then constructed compounds that would lock into the receptor more securely than Gleevec. Investigators at Dana-Farber tested the new compounds to measure their effectiveness against CML in laboratory cell cultures and mice with the disease.

Why does the leukemia become resistant? Evolution within the body. How did they test the new drug? In animal models. They care about model systems because of evolution.